It has been reported that rubrospinal axons will not grow around or through spinal lesions in neonatal kittens although corticospinal axons do so readily. In fact, immature rubral neurons, perhaps unlike cortical ones, die in response to axotomy. It is possible, however, that rubrospinal plasticity can be demonstrated at earlier stages of development, particularly when rubral axons are still growing into the spinal cord. This hypothesis would be difficult to test in commonly used placental mammals since lesions would have to be made prenatally, but should be testable in the North American opossum, since the entire development of its rubrospinal tract occurs postnatally. We propose to use retrograde and orthograde transport techniques to determine whether rubrospinal plasticity can be demonstrated during early stages of development. If, as suggested by pilot studies, rubrospinal plasticity can be documented, we will employ fluorescent markers in single and double-labeling paradigms to determine whether it is a result of axonal regeneration or rerouting of late growing axons. We will also attempt to determine if loss of plasticity correlates with the development of a reactive glial response to injury using immunocytochemical techniques to identify glial fibrillary acidic protein and vimentin. It has been shown that axons from brainstem areas other than the red nucleus also fail to grow around or through spinal lesions in neonatal kittens. It may be, however, that such axons, like those from the red nucleus, are capable of plasticity during earlier stages of development. Indeed it is our guiding hypothesis that all descending spinal pathways are capable of plasticity at some stage of development, but that the critical period for each is different. It is likely that differences in critical period reflect differences in developmental history. We plan to eventually test that hypothesis using several brainstem-spinal pathways, but have proposed to begin with the rubrospinal tract because we know its anatomy and developmental history in the most detail.